The rockefeller university

Event Details

Type

Friday Lecture Series

Speaker(s)

Craig B. Thompson, M.D., president and CEO, Memorial Sloan Kettering Cancer Center

Speaker bio(s)

Past metabolic studies have focused on terminally differentiated cells. These studies suggested that cells maintain bioenergetics through cell-autonomous uptake of available extracellular nutrients, including glucose, lipids and amino acids, and feeding the catabolites of these nutrients into the TCA cycle. However, recent studies using different mammalian cell types have led to the discovery that mammalian cells lack the cell autonomous ability to take up nutrients. When cultured in the absence of receptor ligands, mammalian cells lack the ability to take up sufficient nutrients to sustain ATP synthesis. In mammalian cells the uptake of extracellular nutrients is directed by growth factor signaling.

 

Cellular dependence on ligand-directed nutrient uptake establishes a mechanism by which all cells in multicellular organisms might be rendered dependent on receptor-dependent signals for survival. In addition, the receptors that direct nutrient uptake, when maximally stimulated, can direct a cell to take up glucose in excess of its needs. The major oncogenic determinants of glucose uptake are receptor tyrosine kinases: PI3K, Akt and TOR. Their activation results in the conversion of intermediate metabolism to aerobic glycolysis (the Warburg Effect). The net effect of this metabolism is a diversion of available amino acids into protein synthesis and the establishment of an alternative mitochondrial/cytoplasmic citric acid cycle that converts glucose into lipids. 

 

Although cell growth can be supported effectively by aerobic glycolysis, the conversion from growth to proliferation relies on a cell's ability to switch from glucose to glutamine for the support of bioenergetics. The oncogene myc has recently been implicated in this conversion. This conversion allows glucose metabolites to be redirected into the pentose phosphate shunt and into serine biosynthesis to support nucleotide production and the maintenance of cellular redox.

 

A role for intracellular metabolites in oncogenic signaling and cellular differentiation has also been recently suggested through studies of succinate dehydrogenase and fumarase mutations in cancer. The discovery of cancer-associated mutations in isocitrate dehydrogenase 1 and 2 that produce a novel metabolite, 2-hydroxyglutarate, provides the most compelling example of this principle to date. The implications of these recent findings to carcinogenesis and stem cell biology will be discussed.

Dr. Thompson received his M.D. from the University of Pennsylvania in 1977 and did his internship and residency in internal medicine at Peter Bent Brigham Hospital at Harvard Medical School and at University Hospital in Boston, where he was senior resident. He completed a fellowship at the Fred Hutchinson Cancer Research Center at the University of Washington. Dr. Thompson has held academic appointments at the Uniformed Services University of Health Sciences, the University of Michigan School of Medicine, the University of Chicago and the University of Pennsylvania. In 2010 he joined the faculty of the Weill Cornell Graduate School of Medical Sciences and became president and CEO of Memorial Sloan Kettering Cancer Center. Dr. Thompson is a member of the Institute of Medicine, the National Academy of Sciences, the American Academy of Arts and Sciences, and the Medical Advisory Board of the Howard Hughes Medical Institute.

Open to

Public

Reception

Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge

Contact

Alena Powell

Phone

(212) 327-7745

Sponsor

Alena Powell
(212) 327-7745
apowell@rockefeller.edu

Readings

http://librarynews.rockefeller.edu/?p=3493